Grace Zdesenko

Thesis title: Drug-drug interactions and pharmacogenetics of praziquantel metabolism - implications for variable drug exposure and outcomes in the treatment of schistosomiasis

Precision Medicine DTP

Year of study: 1

  • Institute of Immunology & Infection Research
  • Parasite Immuno-Epidemiology Group

Contact details

Address

Street

Kings Buildings, Ashworth Laboratories
Charlotte Auerbach Road

City
Edinburgh
Post code
EH9 3FL UK

Qualifications

Master of Chemistry in Pharmaceutical Chemistry with a Year in Industry (MChem) (2014-2018)

Year in Industry at AstraZeneca Pharmaceuticals (2016/2017)

Current research interests

Drug Metabolism and Pharmacokinetics Parasite Biology

Past research interests

Pharmaceutical Chemistry - The Synthesis of Novel Benzothiazole Derivatives as Theranostics for use in Cancer Therapies

Project activity

Drug-drug interactions and pharmacogenetics of praziquantel metabolism - implications for variable drug exposure and outcomes in the treatment of schistosomiasis

The main objective of this project is to analyse drug-drug interactions (DDIs) and pharmacogenetics of praziquantel (PZQ) metabolism in the treatment of schistosomiasis. This will involve the evaluation of the role of cytochrome P450 enzymes (CYP) in PZQ metabolism and PZQ pharmacokinetics, focusing on the effect of CYP1A2, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 polymorphisms in African children. To achieve this, PZQ metabolites will be identified and quantified in blood following treatment with the standard dose of PZQ. Furthermore, the analysis of the host genetic variants of CYP enzymes will be performed by quantifying the efficacy of PZQ in schistosome-infected children exhibiting different genetic variants of the CYP genes. The study will evaluate the effect of genetic background on the extent of DDIs by genotyping samples from an ongoing coinfection/comorbidity studies in Zimbabwe, and samples from patients treated for prostate cancer with schistosomiasis. It will also determine the drugs commonly prescribed in people of different age groups treated for helminth infections in Zimbabwe and determine drug coadministration in pharmacy records. The results from this project will inform the tailoring of antihelminthic dosing regimen to maximise efficacy whilst minimising toxicity in people who do not optimally metabolise PZQ due to CYP genetic restriction or DDI.